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www.AJOG.org SMFM Abstracts

41 DIABETES IN PREGNANCY IS ASSOCIATED WITH OXIDATIVE STRESS: LONGITUDINALISOPROSTANE EXPRESSION MATTHEW KIM1, CHANDER ARORA2, ADEGOKE ADENIJI2, CHOBEL3, 1Cedars-Sinai Medical Center, Div of MFM, Dept of Ob/Gyn, Los Angeles,California, 2Cedars-Sinai Medical Center, Los Angeles, California, 3University ofCalifornia, Los Angeles, Los Angeles, California

OBJECTIVE: F2-isoprostanes are prostaglandin F(2 alpha) isomers derivedfrom free radical peroxidation of essential fatty acids such as arachidonic acid.Elevated levels of these markers of oxidative stress have been reported in variouspathological conditions. We sought to measure the levels of F2-isoprostanes inwomen with diabetes during pregnancy to investigate the hypothesis that diabetesin pregnancy is associated with oxidative stress.

STUDY DESIGN: In the Behavior in Pregnancy Study (BIPS), 626 subjects wereevaluated at 18-20 weeks (T1), 28-30 weeks (T2) and 34-36weeks (T3). We identi-fied 26 women from this cohort with diabetes (19 gestational, 7 preexisting). Anequal number of non-diabetic pregnant women who had a negative 50 gram glu-cose challenge test during pregnancy were selected as matched controls. Urinarylevels of F2-isoprostanes were determined by ELISA. Student’s t-test was used forstatistical analysis. Significance was set at p�0.05.

RESULTS: Urinary F2-isoprostanes levels were higher at T2 than T1 in bothgroups. The difference between control and diabetics was a maximum at T2 (2182�211 vs 2780� 187 pg/ml). Although F2-isoprostanes increased steadily during thecourse of pregnancy in control (T1: 1971�280, T2: 2182� 211, T3: 2359� 308 ),the levels were elevated at T2 but declined at T3 in diabetics. In comparison tocontrols, the levels were higher in the diabetic group at all three time points(1971�280 vs 2413� 323 pg/ml at T1, p�.001; 2182� 211vs 2780� 187 pg/ml atT2, p�.001; 2359� 308 vs 2576� 237 pg/ml at T3, p�.01).

CONCLUSION: The results reveal a positive association between urinary F2-iso-prostane concentrations and diabetes suggesting increased oxidative stress in thesesubjects.The decline in the isoprostane level at T3 in diabetics could be due to adecrease in renal excretion but may in fact reflect the impact of improved glycemiccontrol and thereby a lessening of oxidative stress in the maternal-fetal dyad.Thesedata may have clinical significance as they suggest a possible link between diabetesand lipid peroxidation.

0002-9378/$ - see front matterdoi:10.1016/j.ajog.2008.09.571

42 MATERNAL SEVERE UNDERNUTRITION DURING BOTH LATE GESTATION ANDLACTATION PERIOD INDUCE HYPERTENSION IN MALE RAT OFFSPRING HIDENORITAKAHASHI1, KEIYA FUJIMORI1, TOSHIAKI OKAWA1, AKIRA SATO2, 1Fukushima MedicalUniversity, Fukushima, Fukushima, Japan, 2Fukushima Medical University, Ob-stetrics and Gynecology, Fukushima, Fukushima, Japan

OBJECTIVE: Exposure to undernutrition during fetal life has been proposed asan underlying cause of adult hypertension, but the effect of undernutrition duringlactation period is unclear.

Our objective was to investigate the effects of either severe undernutritionduring late gestation or lactation period on blood pressure and the development ofvascular function in male rat offspring.

STUDY DESIGN: We use normal pregnant Wistar rats (Group A), nutritionallyrestricted by feeding with 30% of the normal gestation-matched dietary intake fromday 17 of gestation to delivery (Group B) and 30% restricted after delivery to the endof lactation period (Group C).

The offspring was measured blood pressure at 12 and 24 weeks by using indi-rect tail-cuff method.

Rings of thoracic aorta with intact endothelium from the male offspring of Aand B at 8 weeks, were equilibrated in organ chambers filled with Krebs-Henseleitsolution for isometric tension recording. Concentration-response relationships toNorepinephrine (NE) were obtained in the absence or presence of N(omega)-ni-tro-L-arginine methyl ester (L-NAME) or a selective angiotensin(AT) type-1 re-ceptor blocker (Valsartan). Statically analysis was performed using one-way AN-NOVA.

RESULTS: Body weight was significantly reduced in B offspring compared to Aand C in male offspring at day 1 (p�0.01). At 12 weeks the body weight of offspringof B was no difference to catch up compared to A and C offspring.

Systolic and Diastolic blood pressures were significantly elevated at both 12 and24 weeks in offspring of B � C �A.

Maximal contractions to NE were significantly stimulated by L-NAME in A(p�0.05), but not B offspring. Valsartan significantly inhibited aortic contractionsby NE in B (p�0.05).

CONCLUSION: Severe under nutrition during not only late gestation but alsolactation period induced hypertension in male rat offspring in adulthood. Fetalorigin of adult hypertension might be vascular endothelial dysfunction.

0002-9378/$ - see front matterdoi:10.1016/j.ajog.2008.09.572

Supplemen

43 ADRENAL-MEDIATED PROGRAMMED HYPERTENSION IN PRENATALLY DEHYDRATEDFEMALE OFFSPRING ROY Z. MANSANO1, MINA DESAI1, GUANG HAN1, MICHAEL ROSS1,1Harbor-UCLA Med. Ctr. (LABioMed), Dept. of Ob/Gyn, Torrance, California

OBJECTIVE: Increased fetal glucocorticoid exposure predisposes to hyperten-sion in adult offspring. The mechanism of programmed hypertension may involverenin angiotensin system (RAS) as angiotensin II (AngII) enhances the synthesisand secretion of corticosterone. We have demonstrated that both maternal waterrestriction (WR) and maternal nutrient restriction (NR) result in hypertensiveoffspring. However, WR and NR offspring exhibit differing adult phenotype withWR demonstrating adrenomegaly and upregulation of adrenal AngII receptors. Wehypothesized that programmed adrenal RAS alterations lead to increased cortico-sterone synthesis, resulting in hypertensive offspring. We determined the adrenalprotein expression of the glucocorticoid (GC) receptor and enzymes (11 �-hydrox-ysteroid dehydrogenase types 1 and 2; 11 �HSD) in WR offspring.

STUDY DESIGN: From day 10 to term gestation, control dams received ad libi-tum food and water, dehydrated dams were water restricted (WR) to produceplasma sodium level increment of �6 mEq/l and pair-fed (PF) dams received adlibitum water but were food restricted to amount consumed by the WR dams. Afterdelivery all dams received ad libitum food and water. At 3 weeks of age, adrenalsfrom female offspring were weighed and analyzed for renin, AT1 and AT2 proteinby Western Blot. Data were normalized to GAPDH and is shown as fold change.

RESULTS: At 3 weeks of age, adrenal GC receptor expression was significantlyincreased in WR (2-fold) and decreased in PF (0.5-fold) offspring as compared tocontrols. Consistent with this, the WR offspring showed significant increase incorticosterone-activating, 11�HSD1 (1.7-fold) and corticosterone-inactivating,11�HSD2 (1.4-fold) whereas NR showed no change.

CONCLUSION: The results suggest that programmed hypertension in WR andNR offspring is mediated via differing mechanism. The specific upregulation of GCreceptor and 11�HSD1 suggests corticosterone-mediated mechanism of hyperten-sion in WR offspring.

0002-9378/$ - see front matterdoi:10.1016/j.ajog.2008.09.573

44 MATERNAL REGULATION OF HIGH FAT NOURISHMENT DURING LACTATION PERIODREDUCE A HYPERTENSION OF MALE OFFSPRING HIDENORI TAKAHASHI1, TOSHIAKIOKAWA2, KEIYA FUJIMORI3, AKIRA SATO4, 1Fukushima Med. Univ., Fukushima, Fuku-shima, Japan, 2Fukushima Medical University, Dept. Ob/Gyn, Fukushima, Fuku-shima, Japan, 3Fukusima Meidical University, Obstetrics and Gynecology, Fuku-shima, Fukushima, Japan, 4Fukushima Medical University, Obstetrics andGynecology, Fukushima, Fukushima, Japan

OBJECTIVE: Exposure to undernutrition or high fat nourishment during fetallife has been proposed as an underlying cause of adult hypertension, but the effectof maternal feeding regulation during lactation period on blood pressure of off-spring is unclear.

Our objective was to investigate the effects of either high-fat diet (HFD) duringgestation to lactation period or restrictive fed a HFD during lactation period onblood pressure in male rat offspring.

STUDY DESIGN: We use 3 types pregnant Wistar rats as fed with normal nutri-tion (Group A), with a high fat diet (HFD) during gestation to lactation period(Group B) and with HFD nutritionally restricted by feeding with 30% of the normallactation-matched dietary intake from the day of delivery to the end of lactationperiod (Group C).

The male offspring was measured blood pressure at 12, 24 and 60 weeks byusing indirect tail-cuff method. Statically analysis was performed using one-wayANNOVA.

RESULTS: Body weight was significantly reduced in C offspring compared to Aand B in male offspring at day 28 after delivery (p�0.01). At 12 weeks old, the bodyweight of C offspring was no difference to catch up compared to A and B offspring.

Systolic and Diastolic blood pressures were significantly elevated at all 12, 24and 60 weeks in offspring of B � C �A. (p�0.01, vs. A)

CONCLUSION: Under high-fat nutrition during gestation to lactation periodinduced hypertension in male rat offspring. Maternal high fat environment make ahypertensive offspring, but regulation of fat feeding during lactation period mayreduce adulthood hypertension.

0002-9378/$ - see front matterdoi:10.1016/j.ajog.2008.09.574

t to DECEMBER 2008 American Journal of Obstetrics & Gynecology S159